Germ line mutations in the breast cancer susceptibility gene BRCA2 predispose to early-onset breast cancer, but the function of the nuclear protein encoded by the gene is ill defined. Using the yeast two-hybrid system with fragments of human BRCA2, we identified an interaction with the human DSS1 (deleted in split hand/split foot) gene. Yeast and mammalian two-hybrid assays showed that DSS1 can associate with BRCA2 in the region of amino acids 2472 to 2957 in the C terminus of the protein. Using coimmunoprecipitation of epitope-tagged BRCA2 and DSS1 cDNA constructs transiently expressed in COS cells, we were able to demonstrate an association. Furthermore, endogenous BRCA2 could be coimmunoprecipitated with endogenous DSS1 in MCF7 cells, demonstrating an in vivo association. Apparent orthologues of the mammalian DSS1 gene were identified in the genome of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Yeast strains in which these DSS1-like genes were deleted showed a temperature-sensitive growth phenotype, which was analyzed by flow cytometry. This provides evidence for a link between the BRCA2 tumor suppressor gene and a gene required for completion of the cell cycle.

1. Extracellular recordings from rat mesenteric paravascular nerve bundles were made in order to characterize the responses of different populations of afferents supplying the small intestine to intravenous cholecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70% of mesenteric nerve bundles contained CCK‐sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/‐ 0.3 impulses s‐1) and showed a 14‐fold increase in firing at the peak of the response to 50 pmol CCK with the overall response lasting several minutes. The onset of the response occurred after a latency of (3.9 +/‐ 0.1 s) following i.v. administration of CCK, which corresponds largely to the circulation delay in these animals. The threshold dose of CCK was < 5 pmol. 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg‐1) and by chronic subdiaphragmatic vagotomy performed 10‐14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents. 4. Evidence that CCK‐sensitive afferents had mucosal receptive fields was indicated by the lack of any response to luminal distension and the sensitivity of the CCK response to luminal anaesthesia. Furthermore, CCK‐sensitive afferents responded to luminal hydrochloric acid (50 mM) in a slowly adapting manner. The response to acid was significantly reduced (P < 0.005), but not abolished, by devazepide at a time when the response to exogenous CCK had been completely eliminated. 5. The exquisite sensitivity of some vagal mucosal afferents to CCK suggests that they may play a physiological role in the reflex and behavioural consequences of CCK release from the small intestine, possibly acting in a paracrine fashion. However, this sensitivity to CCK represents only one aspect of the broad chemosensitivity of these mucosal afferents and is not an obligatory component of the signal transduction pathway.

-Fishery independent indices of spawning biomass of Atlantic bluefin tuna in western North Atlantic Ocean are presented which utilize National Marine Fisheries Service ichthyoplankton survey data collected from 1977 through 2007 in the Gulf of Mexico. Indices were developed using similarly standardized data from which previous indices were developed (i.e. abundance of larvae with a first daily otolith increment formed per 100 m 2 of water sampled with bongo gear). Indices were also developed for the first time from standardized data collected with neuston gear [i.e. abundance of 5-mm larvae (i.e. seven-day-old larvae) per 10 minute tow]. Indices of larval abundance were developed using delta-lognormal models, including following covariates: time of day, time of month, area sampled and year. Due to the large frequency of zero catches during ichthyoplankton surveys, a zero-inflated delta-lognormal approach was also used to develop indices. Finally, a multivariate delta-lognormal approach was employed to develop indices of annual abundance based on both bongo and neuston catches. The results of these approaches were compared with one another and with other indices of larval abundance previously developed for the Gulf of Mexico. Residual analyses indicated that abundance indices of Atlantic bluefin tuna larvae were more appropriately developed from bongo-collected data through the zero-inflated delta-lognormal approach than other data sets and modeling approaches. Also, when modeling bongocollected data with the zero-inflated delta-lognormal approach, the index values increased, indicating some correction for zero-inflation, and their variability decreased as compared to indices developed with the delta-lognormal approach. Key words:Mathematical models / Multivariate analysis / Fish larvae / Atlantic Ocean Résumé -Des indices d'abondance, indépendants de la biomasse « féconde » du thon rouge de Atlantique nord-ouest, sont présentés en utilisant les données ichtyoplanctoniques des campagnes océanographiques américaines (NMFS) collectées dans le golfe du Mexique de 1977 à 2007. Des indices sont développés en utilisant des données standardisées à partir des indices antérieurs (abondance des larves dont les otolithes présentent une seule zone d'accroissement journalier, par 100 m 2 d'eau échantillonnée avec un filet bongo). Des indices sont aussi développés pour la première fois à partir de données collectées avec un filet à neuston et standardisées (abondance de larves de 5-mm, âgées de 7 jours) par trait de 10 minutes. Des indices d'abondance larvaire sont développés en utilisant des distributions delta-log normales, incluant les covariables suivantes : jour, mois, zone échantillonnée, année. Dû à la fréquence importante de captures nulles durant ces campagnes d'ichtyoplancton, un ajustement, au moyen d'une distribution delta-log normale pour des données présentant une grande quantité de valeurs nulles, est aussi utilisé pour développer des indices. Finalement, une approche delta-log normale multivariée est e...

No abstract